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Differential capacity of human interleukin-4 and interferon-α monocyte-derived dendritic cells for cross-presentation of free versus cell-associated antigen.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2015 Nov; Vol. 64 (11), pp. 1419-27. Date of Electronic Publication: 2015 Jul 28. - Publication Year :
- 2015
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Abstract
- Dendritic cells (DC) vaccination is a potent therapeutic approach for inducing tumor-directed immunity, but challenges remain. One of the particular interest is the induction of an immune response targeting multiple (unknown) tumor-associated antigens (TAA), which requires a polyvalent source of TAA. Previously, we described the preferred use of apoptotic cell-derived blebs over the larger apoptotic cell remnants, as a source of TAA for both in situ loading of skin-resident DC and in vitro loading of monocyte-derived DC (MoDC). Recent reports suggest that MoDC cultured in the presence of GM-CSF supplemented with IFNα (IFNα MoDC), as compared to IL-4 (IL-4 MoDC), have an increased capacity to cross-present antigen to CD8(+) T cells. As culture conditions, maturation methods and antigen sources differ between the conducted studies, we analyzed the functional differences between IL-4 MoDC and IFNα MoDC, loaded with blebs, in a head-to-head comparison using commonly used protocols. Our data show that both MoDC types are potent (cross-) primers of CD8(+) T cells. Whereas IFNα MoDC were more potent in their capacity to cross-present a 25-mer MART-1 synthetic long peptide (SLP) to a MART-1aa26-35 recognizing CD8(+) T cell line, IL-4 MoDC proved more potent cross-primers of antigen-specific CD8(+) T cells when loaded with blebs. The latter is likely due to the observed greater capacity of IL-4 MoDC to ingest apoptotic blebs. In conclusion, our data indicate the use of IFNα MoDC over IL-4 MoDC in the context of DC vaccination with SLP, whereas IL-4 MoDC are preferred for vaccination with bleb-derived antigens.
- Subjects :
- Antigen Presentation drug effects
Cancer Vaccines immunology
Dendritic Cells drug effects
Humans
MART-1 Antigen immunology
T-Lymphocytes immunology
Vaccination
Antigen Presentation immunology
Antigens, Neoplasm immunology
Cross-Priming
Dendritic Cells immunology
Interferon-alpha pharmacology
Interleukin-4 pharmacology
Monocytes cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0851
- Volume :
- 64
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 26216454
- Full Text :
- https://doi.org/10.1007/s00262-015-1741-1